Potent cyclic urea HIV protease inhibitors with 3-aminoindazole P2/P2' groups

Article abstract of DOI:10.1016/S0960-894X(98)00118-8

Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a K(i) < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.